2-Ethynylaziridines as chiral carbon nucleophiles: Stereoselective synthesis of 1,3-amino alcohols with three stereocenters via allenylindium reagents bearing a protected amino group

Article abstract of DOI:10.1021/jo005756v

Allenylindium reagents bearing a protected amino group were effectively prepared from N-protected 3-alkyl-2-ethynylaziridines by treatment with InI in the presence of Pd(PPh₃)₄ and H₂O. Stereo-selective addition of the allenylindium to aliphatic or aromatic aldehydes affords 1,3-amino alcohols bearing three contiguous chiral centers: while 2,3-trans-2-ethynylaziridines yield syn,syn-2-ethynyl-1,3-amino alcohols predominantly, 2,3-cis-aziridines give anti,syn isomers selectively. Synthesis of highly substituted ethynylazetidines is also described.

Full text of DOI:10.1021/jo005756v

J . Org. Chem. 2001, 66, 1867-1875
1867
2-Eth yn yla zir id in es a s Ch ir a l Ca r bon Nu cleop h iles:
Ster eoselective Syn th esis of 1,3-Am in o Alcoh ols w ith Th r ee
Ster eocen ter s via Allen ylin d iu m Rea gen ts Bea r in g a P r otected
Am in o Gr ou p
Hiroaki Ohno, Hisao Hamaguchi, and Tetsuaki Tanaka*
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka,
Suita, Osaka 565-0871, J apan
t-tanaka@phs.osaka-u.ac.jp
Received December 4, 2000
Allenylindium reagents bearing a protected amino group were effectively prepared from N-protected
3-alkyl-2-ethynylaziridines by treatment with InI in the presence of Pd(PPh3)4 and H2O. Stereo-
selective addition of the allenylindium to aliphatic or aromatic aldehydes affords 1,3-amino alcohols
bearing three contiguous chiral centers: while 2,3-trans-2-ethynylaziridines yield syn,syn-2-ethynyl-
1,3-amino alcohols predominantly, 2,3-cis-aziridines give anti,syn isomers selectively. Synthesis of
highly substituted ethynylazetidines is also described.
Sch em e 1
In tr od u ction
Aziridines, three-membered azacycles, are widely used
as carbon electrophiles since they easily undergo ring-
opening reactions with a wide range of nucleophiles in a
stereoselective manner.1 Successful syntheses of chiral
aziridines2,3 in recent years make them more valuable
intermediates for synthesis of various compounds bearing
a nitrogen atom.4,5 In contrast, the reactions of aziridines
as carbon nucleophiles are scarcely known with the
exception of a few examples: (1) aziridinyl anion re-
agents,6 which are known as useful precursors of highly
substituted aziridines, and (2) ring-opening reaction of
aziridines with lithium naphthalenide.7,8 The latter is an
interesting reaction for reductive coupling of aziridines
and electrophiles, in which stereochemistries of aziridines
were not reflected in the products due to the configura-
tional lability of the alkyllithium species.
To demonstrate the utility of aziridines as chiral carbon
nucleophiles, we planned to synthesize 2-ethynyl-1,3-
amino alcohol 2 from ethynylaziridine 1 via allenylin-
dium reagent A bearing an amino group (Scheme 1).
Synthesis of the related amino alcohols bearing an
ethynyl group was reported by J acobi and co-workers,
utilizing a combination of a modified Nicholas reaction
and Curtius rearrangement.9 However, our newly planned
synthesis of 2 would have an advantage in ease of
(1) For recent reviews of aziridines, see: (a) Padwa, A.; Woolhouse,
A. D. In Comprehensive Heterocyclic Chemistry; Lwowski, W., Ed.;
Pergamon: Oxford, 1984; Vol. 7, pp 47-93. (b) Tanner, D. Angew.
Chem., Int. Ed. Engl. 1994, 33, 599. (c) Ibuka, T. Chem. Soc. Rev. 1998,
27, 145. (d) Atkinson, R. S. Tetrahedron 1999, 55, 1519. (e) Nadin, A.
J . Chem. Soc., Perkin Trans. 1 1999, 2553. (f) Mitchinson, A.; Nadin,
A. J . Chem. Soc., Perkin Trans. 1 2000, 2862. (g) McCoull, W.; Davis,
F. A. Synthesis 2000, 1347.
(5) (a) Ibuka, T.; Nakai, K.; Habashita, H.; Hotta, Y.; Fujii, N.;
Mimura, N.; Miwa, Y.; Taga, T.; Yamamoto, Y. Angew. Chem., Int. Ed.
Engl. 1994, 33, 652. (b) Ibuka, T.; Mimura, N.; Aoyama, H.; Akaji, M.;
Ohno, H.; Miwa, Y.; Taga, T.; Nakai, K.; Tamamura, H.; Fujii, N.;
Yamamoto, Y. J . Org. Chem. 1997, 62, 999. (c) Ibuka, T.; Mimura, N.;
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Y.; Taga, T.; Fujii, N.; Yamamoto, Y. J . Org. Chem. 1997, 62, 2982. (d)
Ohno, H.; Mimura, N.; Otaka, A.; Tamamura, H.; Fujii, N.; Ibuka, T.;
Shimizu, I.; Satake, A.; Yamamoto, Y. Tetrahedron 1997, 53, 12933.
(e) Toda, A.; Aoyama, H.; Mimura, N.; Ohno, H.; Fujii, N.; Ibuka, T. J .
Org. Chem. 1998, 63, 7053. (f) Tamamura, H.; Yamashita, M.;
Nakajima, Y.; Sakano, K.; Otaka, A.; Ohno, H.; Ibuka, T.; Fujii, N. J .
Chem. Soc., Perkin Trans. 1 1999, 2983. (g) Ohno, H.; Toda, A.; Miwa,
Y.; Taga, T.; Fujii, N.; Ibuka, T. Tetrahedron Lett. 1999, 40, 349. (h)
Ohno, H.; Toda, A.; Fujii, N.; Takemoto Y.; Tanaka, T.; Ibuka, T.
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Osborn, H. M. I.; Sweeney, J . Tetrahedron: Asymmetry 1997, 8, 1693.
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Sagasser, I.; Henniges, H.; Sharpless, K. B. J . Am. Chem. Soc. 1998,
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1990, 55, 4683. (b) Pearson, W. H.; Bergmeier, S. C.; Degan, S.; Lin,
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10.1021/jo005756v CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/06/2001

1868 J . Org. Chem., Vol. 66, No. 5, 2001
Ohno et al.
introduction of various alkyl or aryl group (R2) by simply
changing the aldehydes. While this study was in progress,
the pioneering work on allenylindium reagents by Mar-
shall and co-workers appeared.10 Thus, treatment of
propargylic mesylates with InI and aldehydes in the
presence of catalytic palladium(0) affords ethynyl alcohols
in good stereoselectivities via allenylindium reagents.
However, it is a matter of interest to investigate the
utility of ethynylaziridines as a precursor of an allenylin-
dium reagent, the stability and reactivity of the alle-
nylindium bearing an amino group, and regio- and
stereoselectivity in both the reagent formation and ad-
dition to aldehydes. Herein we detail a highly stereose-
lective synthesis of the 2-ethynyl-1,3-amino alcohol 2 by
umpolung of ethynylaziridines 1 with indium(I) and a
catalytic amount of palladium(0).11,12
Sch em e 2a
a
Abbreviations: Mts ) 2,4,6-trimethylphenylsulfonyl; Mtr )
4-methoxy-2,3,6-trimethylphenylsulfonyl; TBS
methylsilyl.
) tert-butyldi-
Sch em e 3a
Resu lts a n d Discu ssion
Syn t h esis of E t h yn yla zir id in es fr om Na t u r a l
Am in o Acid s. It is well documented that the reactivity
of N-unsubstituted or N-alkylaziridines is relatively low;
hence, activation by the introduction of an electron-
withdrawing protecting group on the nitrogen atom of
the aziridine is required. The choice of arylsulfonyl (Mts,
Mtr, or Ts) or tert-butoxycarbonyl (Boc) as the activating
group was based on the convenience of the introduction
and deprotection of these groups.
According to our reported procedure,13 we synthesized
the 2-ethynylaziridines 3a -e and 4a -e via protected
amino aldehydes derived from L-valine, L-phenylalanine,
or L-serine (Scheme 2).14
Ethynylaziridines 3f and 4f bearing a methyl substitu-
ent at C-3 were synthesized as shown in Scheme 3. The
compound 5 was readily prepared from D-allothreonine
following the literature.15 Protection of 5 gave the silyl
ether 6, which was reduced by DIBAL-H to yield 7 in
64% yield. Successive treatment of the alcohol 7 with
oxalyl chloride-DMSO-N,N-diisopropylethylamine, t-
BuOK-dibromomethyltriphenylphosphonium bromide,16
and t-BuOK gave the alkyne 8 in 44% overall yield.
Deprotection of the TBS group of 8 by tetrabutylammo-
a
Reagents and conditions: (a) TBSCl, imidazole, DMF; (b)
DIBAL-H, toluene; (c) (COCl)2, DMSO, CH2Cl2, then (i-Pr)2NEt;
(d) Ph3P+CHBr2‚Br-, t-BuOK, THF then t-BuOK; (e) TBAF, THF;
(f) diethyl azodicarboxylate, PPh3, THF.
nium fluoride gave 9, which was readily converted into
the desired 2,3-trans-2-ethynylaziridine 3f by dehydra-
tion under Mitsunobu conditions.13b,17 Similarly, the 2,3-
cis-aziridine 4f was synthesized from L-threonine starting
from the known compound 1018 (see the Experimental
Section).
Stereochemical assignments of the synthesized 3f and
4f were readily made by comparison of J values of the
ring protons. The trans-ethynylaziridine 3f shows smaller
J Hab values (J ) 4.5 Hz) than that of cis isomer 4f (J )
6.9 Hz).13b
(9) (a) J acobi, P. A.; Zheng, W. Tetrahedron Lett. 1993, 34, 2581.
(b) J acobi, P. A.; Murphree, S.; Rupprecht, F.; Zheng, W. J . Org. Chem.
1996, 61, 2413. See also, (c) Liu, C.; Hashimoto, Y.; Saigo, K.
Tetrahedron Lett. 1996, 37, 6177.
(10) (a) Marshall, J . A.; Grant, C. M. J . Org. Chem. 1999, 64, 696.
(b) Marshall, J . A.; Grant, C. M. J . Org. Chem. 1999, 64, 8214. (c)
Marshall, J . A.; J ohns, B. A. J . Org. Chem. 2000, 65, 1501. (d) Marshall,
J . A. Chem. Rev. 2000, 100, 3163.
P r ep a r a tion of Allen ylin d iu m Rea gen ts Bea r in g
a P r otected Am in o Gr ou p . Having synthesized the
requisite substrates, we initiated work on preparation
of the allenylindium reagent from the ethynylaziridines
3a (Scheme 4 and Table 1). The desired reagent could
not be prepared using indium powder under various
reaction conditions in the presence or absence of a
palladium catalyst. Formation of allenylindium was
observed using InI in DMF in the presence of Pd(PPh3)4,
yielding an inseparable mixture of 13 and 14 after
hydrolysis (54% yield; 13:14 ) 84:16; Table 1, entry 1).
Other solvents such as MeOH or THF were less effective
(entries 2 and 3); however, we found that a promising
result was obtained using THF-H2O (1:1) as solvent
(89% yield, 13:14 ) 91:9; entry 4). Although one of
(11) A portion of this study was reported in a preliminary com-
munication: Ohno, H.; Hamaguchi, H.; Tanaka, T. Org. Lett. 2000, 2,
2161.
(12) For related work: (a) Masuyama, Y.; Watabe, A.; Ito, A.;
Kurusu, Y. Chem. Commun. 2000, 2009. (b) Araki, S.; Kamei, T.;
Hirashita, T.; Yamamura, H.; Kawai, M. Org. Lett. 2000, 2, 847. (c)
Sakamoto, T.; Takahashi, K.; Yamazaki, T.; Kitazume, T. J . Org. Chem.
1999, 64, 9467. (d) Mikami, K.; Yoshida, A.; Matsumoto, S.; Feng, F.;
Matsumoto, Y. Tetrahedron Lett. 1995, 36, 907. (e) Tamaru, Y.; Goto,
S.; Tanaka, A.; Shimizu, M.; Kimura, M. Angew. Chem., Int. Ed. Engl.
1996, 35, 878. (f) Isaac, M. B.; Chan, T.-H. J . Chem. Soc., Chem.
Commum. 1995, 1003.
(13) (a) Ohno, H.; Toda, A.; Fujii, N.; Ibuka, T. Tetrahedron:
Asymmetry 1998, 9, 3929. (b) Ohno, H.; Toda, A.; Takemoto, Y.; Fujii,
N.; Ibuka, T. J . Chem. Soc., Perkin Trans. 1 1999, 2949.
(14) Other synthesis of ethynylaziridines: (a) Li, A.-H.; Zhou, Y.-
G.; Dai, L.-X.; Hou, X.-L.; Xia, L.-J .; Lin, L. Angew. Chem., Int. Ed.
Engl. 1997, 36, 1317. (b) Chemla, F.; Hebbe, V.; Normant, J . F.
Tetrahedron Lett. 1999, 40, 8093.
(15) Fujii, N.; Nakai, K.; Habashita, H.; Hotta, Y.; Tamamura, H.;
Otaka, A.; Ibuka, T. Chem. Pharm. Bull. 1994, 42, 2241.
(16) (a) Michel, P.; Gennet, D.; Rassat, A. Tetrahedron Lett. 1999,
40, 8575. See also, (b) Wolkoff, P. Can. J . Chem. 1975, 53, 1333.
(17) Pfister, J . R. Synthesis 1984, 969.
(18) Ohno, H.; Ishii, K.; Honda, A.; Tamamura, H.; Fujii, N.;
Takemoto, Y.; Ibuka, T. J . Chem. Soc., Perkin Trans. 1 1998, 3703.

2-Ethynylaziridines as Chiral Carbon Nucleophiles
J . Org. Chem., Vol. 66, No. 5, 2001 1869
Ta ble 1. P r ep a r a tion of th e Allen ylin d iu m Rea gen ts fr om th e Azir id in es 3a a n d 4a a
reaction
time (min)
entry
aziridine
catalyst
solvent
yieldb (%)
ratio 13:14c
1
2
3
4
5
6
7
3a
3a
3a
3a
3a
3a
3a
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
DMF
MeOH
THF
THF-H2O (1:1)
THF, H2O (1 equiv)
THF-HMPA (4:1)
THF-HMPA (4:1),
H2O (1 equiv)
20
600
90
30
90
54
trace
34
89
41
84:16
ND
86:14
91:9
85:15
ND
90:10
90
20
trace
83
8
3a
none
THF-HMPA (4:1),
H2O (1 equiv)
90
6d
ND
9
10
4a
4a
Pd(PPh3)4
Pd(PPh3)4
THF-H2O (1:1)
THF-HMPA (4:1),
H2O (1 equiv)
30
20
89
76
91:9
91:9
a
All reactions were carried out at room temperature using palladium catalyst (5 mol %), InI (1.5 equiv). After being stirred at room
temperature for the indicated time, the resulting allenylindium reagents were quenched with 1N HCl. Combined isolated yields. c Ratios
b
were determined by 1H NMR (270 MHz). A quite similar result was obtained using freshly opened equipment, which means that some
d
allenylindium could be formed in the absence of palladium catalyst.10
Ta ble 2. Effects of Solven t a n d Ca ta lyst in th e
In d iu m (I)-Med ia ted Red u ctive Cou p lin g Rea ction of th e
Eth yn yla zir id in e 3c a n d Isobu tyr a ld eh yd ea
Sch em e 4
entry
catalyst
Pd(PPh3)4
Pd(dppf)Cl2‚CH2Cl2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
solvent
yieldb (%)
1
2
3
4
5
THF-HMPA (4:1)
THF-HMPA (4:1)
THF
THF-H2O (10:1)
THF-H2O (1:1)
62
61
53
46
48
Marshall’s conditions [InI, Pd(PPh3)4, THF-HMPA]10
was not effective for the reagent formation from the
ethynylaziridine 3a (entry 6), a similar result to THF-
H2O (entry 4) was obtained using THF-HMPA (4:1) in
the presence of one equivalent of H2O (entry 7). The
corresponding 2,3-cis-aziridine 4a also gave the allenylin-
dium reagent by treatment with InI and Pd(PPh3)4 in
THF-H2O (entry 9) or THF-HMPA-H2O (entry 10).
Interestingly, it was found that the presence of H2O is
an important factor for the effective formation of the
allenylindium bearing a protected amino group from
2-ethynylaziridines.
Red u ctive Cou p lin g Rea ction of 2-Eth yn yla zir i-
d in es w ith Ald eh yd es. To reveal the synthetic utility
of allenylindium reagents bearing a protected amino
group as chiral carbanions, we investigated their coupling
reaction with aldehydes. A brief survey of the results with
the aziridine 3c and isobutyraldehyde is summarized in
Table 2. The aziridine 3c was treated with InI (1.3 equiv),
isobutyraldehyde (1.5 equiv), and H2O (1 equiv) in THF-
HMPA (4:1) in the presence of Pd(PPh3)4 (5 mol %) or
Pd(dppf)Cl2‚CHCl3 (5 mol %) to afford the desired amino
alcohol 15 (62% and 61% yield, respectively). In both
cases, the syn,syn adduct was the only isomer isolated
(>97:3). To our dismay, THF or a mixed solvent of THF-
H2O was less effective for the addition reaction toward
the aldehyde (entries 3-5).
a
All reactions were carried out at room temperature using
palladium catalyst (5 mol %), InI (1.3 equiv), H2O (1 equiv), and
b
isobutyraldehyde (1.5 equiv). Isolated yields.
anti,syn adduct 21 was isolated (20:21 ) 93:7). It turned
out that the steric bulk of the substituent at C-3 of
ethynylaziridines exerts a significant influence on the
reactivity and selectivity of the allenylindium reagents:
allenylindium from the 2-ethynylaziridines 3e and 3f
bearing a relatively small substituent at C-3 was found
to be more reactive toward the aldehydes yielding the
corresponding amino alcohols 19 and (20 and 21) in
higher yields, while the allenylindiums from 2,3-trans-
2-ethynylaziridines 3a and 3b bearing a bulky isopropyl
group showed lower reactivities, giving the corresponding
amino alcohols 16 and 17 in lower yields (42% and 43%,
respectively).
Next, the same reactions were conducted with the 2,3-
cis-aziridines 4a -f (Scheme 6). In sharp contrast to 2,3-
trans-2-ethynylaziridines, it was found that 2,3-cis-
aziridines 4a -f gave anti,syn adducts 22-26 and 21
exclusively or predominantly under the identical reaction
conditions. In the cases of 4a -e, only the anti,syn-
adducts were isolated. Not surprisingly, the cis-aziridine
4f bearing a methyl substituent at C-3 afforded a
separable mixture of 21 and 20 (21:20 ) 87:13) in high
yield (79%), in line with the trans-aziridine 3f (Scheme
5).
Similarly, 2,3-trans-aziridines 3a -e also gave syn,syn
adducts 16-19 as the only isolable isomers. The results
are summarized in Scheme 5. Substituents such as a
benzyl (3c and 3d ) or silyloxy group (3e) caused no
undesired side reaction. When 3-methyl-2-ethynylaziri-
dine 3f was employed, however, a small amount of
Other aromatic or aliphatic aldehydes could be analo-
gously used for the present coupling reaction (Schemes
7 and 8). For example, the reaction of 2,3-trans-aziridine
3d with benzaldehyde or acetaldehyde yielded 27 or 28,

1870 J . Org. Chem., Vol. 66, No. 5, 2001
Ohno et al.
Sch em e 5a
Sch em e 7a
a
Conditions: Pd(PPh3)4 (5 mol %), InI (1.3 equiv), H2O (1 equiv),
aldehyde (1.5 equiv), THF/HMPA ) 4:1, rt, 4 h.
Sch em e 8a
a
Reaction conditions: Pd(PPh3)4 (5 mol %), InI (1.3 equiv), H2O
(1 equiv), isobutyraldehyde (1.5 equiv).
Sch em e 6a
a
Conditions: Pd(PPh3)4 (5 mol %), InI (1.3 equiv), H2O (1 equiv),
aldehyde (1.5 equiv), THF/HMPA ) 4:1, rt, 4 h.
) 93:7). It should be noted that, when employing acetal-
dehyde as an electrophile, although the 2,3-trans-aziri-
dine 3d yielded only syn,syn-28, the corresponding 2,3-
cis-aziridine 4d gave a mixture of the anti,syn-32 and
anti,anti-33 (32:33 ) 88:12; Scheme 8). Similarly, the cis-
aziridine 4f yielded a small amount of anti,anti isomer
36 (Scheme 8; 30:36:29 ) 81:11:8) which was not
observed in the reaction mixture using trans-3f (Scheme
7).
Thus, it was found that, whereas 2,3-trans-2-ethynyl-
aziridines yield syn,syn-2-ethynyl-1,3-amino alcohols pre-
dominantly or exclusively by their treatment with InI,
H2O, and aldehydes in the presence of catalytic pal-
ladium(0), 2,3-cis-aziridines give anti,syn isomers selec-
tively under the same reaction conditions.
a
Reaction conditions: Pd(PPh3)4 (5 mol %), InI (1.3 equiv), H2O
(1 equiv), isobutyraldehyde (1.5 equiv).
All the isomeric mixtures in Schemes 5-8 except for
(32 and 33) were easily separated by flash column
respectively, in good yields (Scheme 7). As expected,
reaction of the 3-methyl-2-ethynylaziridine 3f with acet-
aldehyde gave syn,syn-amino alcohol 29 predominantly
along with a small amount of anti,syn isomer 30 (29:30
chromatography and fully characterized by 1H NMR, 13
C
NMR, IR, and mass spectra or elemental analyses.
Although the mixture of 32 and 33 was inseparable at

2-Ethynylaziridines as Chiral Carbon Nucleophiles
J . Org. Chem., Vol. 66, No. 5, 2001 1871
Sch em e 9a
a
Reaction conditions: (a) Pd(dppf)Cl2‚CHCl3 (5 mol %), InI (1.3
equiv), H2O (1 equiv), benzaldehyde (1.5 equiv); (b) NaH (1.5
equiv), THF/DMF (1:1), rt, 1.5 h.
this stage, these two isomers were isolated and charac-
terized after derivatization into their silyl ethers 34 and
35 (see the Experimental Section).
F igu r e 1. Plausible mechanistic pathway.
Deter m in a tion of Ster eoch em istr ies of 2-Eth yn yl-
1,3-a m in o Alcoh ols. Stereochemical assignments for the
synthesized diastereomeric amino alcohols were readily
made by their transformation into tetrahydro-1,3-oxazin-
2-one derivatives as shown in Scheme 9. The amino
alcohol 37, prepared by the reaction of the 2,3-trans-2-
ethynylaziridine 3b with benzaldehyde, was treated with
NaH to give the tetrahydro-1,3-oxazin-2-one 38. Irradia-
tion of the signal of 6-H led to NOE enhancement of the
signals of 4-H and 5-H (7.6% for 4-H and 6.4% for 5-H).
Similarly, in the case of 40 derived from 2,3-cis-aziridine
4b, NOE was observed between [5-H and 6-H (6.6%)] and
[5-H and 1′-H (1.8%)], as shown in structure 40 (Scheme
9).19
One plausible mechanism for the present reductive
coupling reaction is shown in Figure 1. Attack of pal-
ladium(0) to ethynylaziridine from the opposite side of
the C-N bond of the aziridine ring would produce the
allenylpalladium(II) intermediate 42, which would be
converted into 43 by transmetalation with InI retaining
the stereochemistry.10 Coordination of the indium atom
with carbonyl oxygen of aldehyde enables the approach
of the aldehyde from the same side of the indium atom.20
Since the unfavorable steric interaction between the
substituents R and R1 destabilizes 44, the syn,syn-45 will
be obtained as a major isomer via 43. Although the exact
role of H2O is unclear, protonation of the aza-anionic
species 42 by H2O is assumed to be an important factor
for the effective formation of the allenylindium from
2-ethynylaziridines. For example, protonation of 42 might
shift the equilibrium between 41 and 42 toward the
latter. Similarly, the predominant formation of the
anti,syn-amino alcohol 51 from the 2,3-cis-2-ethynylaziri-
dine 47 can be rationalized by an analogous pathway as
depicted in Figure 1.
Syn th esis of High ly-Su bstitu ted Azetid in es u n -
d er Mitsu n obu Con d ition s. Chiral azetidines can be
seen in several biologically active compounds,21 and
recently, they have attracted much attention due to their
efficacy as chiral ligands for asymmetric syntheses.22,23
To expand the synthetic utility of our novel reaction and
to confirm the stereochemistries more strictly, we finally
investigated the synthesis of highly substituted azeti-
dines bearing three chiral centers under Mitsunobu
conditions. Unfortunately, treatment of the syn,syn-
amino alcohol 15 with diethyl azodicarboxylate and
triphenylphosphine in THF afforded the desired azetidine
53 in poor yield (9%). The major product was the
homoallylic amine 54 produced by â-elimination of the
hydroxy group. However, the syn,syn-amino alcohols 27
and 29 yielded the desired ethynylazetidines 55 and 56,
respectively, in high yields. While the anti,anti-36 gave
(21) (a) Dolle´, F.; Dolci, L.; Valette, H.; Hinnen, F.; Vaufrey, F.;
Guenther, I.; Fuseau, C.; Coulon, C.; Bottlaender, M.; Crouzel, C. J .
Med. Chem. 1999, 42, 2251. (b) Holladay, M. W.; Wasicak, J . T.; Lin,
N.-H.; He, Y.; Ryther, K. B.; Bannon, A. W.; Buckley, M. J .; Kim, D. J .
B.; Decker, M. W.; Anderson, D. J .; Campbell, J . E.; Kuntzweiler, T.
A.; Donnelly-Roberts, D. L.; Piattoni-Kaplan, M.; Briggs, C. A.;
Williams, M.; Arneric, S. P. J . Med. Chem. 1998, 41, 407. (c) Knapp,
S.; Dong, Y. Tetrahedron Lett. 1997, 38, 3813.
(22) (a) Doyle, M. P.; Davies, S. B.; Hu, W. Chem. Commun. 2000,
867. (b) Shi, M.; J iang, J .-K. Tetrahedron: Asymmetry 1999, 10, 1673.
(c) Starmans, W. A. J .; Walgers, R. W. A.; Thijs, L.; de Gelder, R.; Smits,
J . M. M.; Zwanenburg, B. Tetrahedron 1998, 54, 4991. (d) Starmans,
W. A. J .; Thijs, L.; Zwanenburg, B. Tetrahedron 1998, 54, 629.
(23) For recent syntheses of azetidines, see: (a) Concello´n, J . M.;
Bernad, P. L.; Pe´rez-Andre´s, J . A. Tetrahedron Lett. 2000, 41, 1231.
(b) Anzai, M.; Toda, A.; Ohno, H.; Takemoto, Y.; Fujii, N.; Ibuka, T.
Tetrahedron Lett. 1999, 40, 7393. (c) Rutjes, F. P. J . T.; Tjen, K. C. M.
F.; Wolf, L. B.; Karstens, W. F. J .; Schoemaker, H. E.; Hiemstra, H.
Org. Lett. 1999, 1, 717. (d) Starmans, W. A. J .; Doppen, R. G.; Thijs,
L.; Zwanenburg, B. Tetrahedron: Asymmetry 1998, 9, 429. (e) Wessig,
P.; Schwarz, J . Helv. Chim. Acta 1998, 81, 1803. (f) Alcaide, B.; Salgado,
N. R.; Sierra, M. A. Tetrahedron Lett. 1998, 39, 467.
(19) Stereochemistries of 32 and 33 were determined by their
transformation into a diastereomeric mixture of the corresponding
azetidines and subsequent NOE experiment, in a similar way as shown
in Scheme 10 (see the Supporting Information).
(20) Paquette, L. A.; Rothhaar, R. R. J . Org. Chem. 1999, 64, 217.

1872 J . Org. Chem., Vol. 66, No. 5, 2001
Ohno et al.
Sch em e 10a
Optical rotations were measured in CHCl3. For flash chroma-
tography, silica gel 60 H (silica gel for thin-layer chromatog-
raphy, Merck) or silica gel 60 (finer than 230 mesh, Merck)
was employed. InI is available from the Aldrich and was
crushed before use.
Known compounds 3a -e,13 4a -e,13 5,15 and 1018 were
synthesized according to the literature.
Meth yl (2R,3R)-3-ter t-Bu tyld im eth ylsilyloxy-2-[N-(4-
m eth ylp h en ylsu lfon yl)a m in o]bu ta n oa te (6). To a stirred
mixture of 5 (5.60 g, 19.5 mmol) and imidazole (4.10 g, 60.1
mmol) in CHCl3 (17 mL) and DMF (11 mL) at room temper-
ature was added tert-butyldimethylsilyl chloride (5.31 g, 35.4
mmol) with stirring at 0 °C, and stirring was continued
overnight. Water was added, and the whole was extracted with
Et2O. The extract was washed successively with 4% HCl,
water, saturated NaHCO3, and brine and then dried over
MgSO4. Concentration under reduced pressure gave an oily
residue, which was purified by flash chromatography over
silica gel with hexane-EtOAc (2:1) to give 6 (6.65 g, 85% yield)
as colorless crystals: mp 72-74 °C (Et2O-hexane); [R]26
D
-13.9 (c 1.00, CHCl3); IR (KBr) cm-1 3267 (NHSO2), 1743 (Cd
1
O), 1348 (NHSO2); H NMR (300 MHz, CDCl3) δ 0.02 (s, 3H,
SiMe), 0.03 (s, 3H, SiMe), 0.82 (s, 9H, CMe3), 1.23 (d, J ) 6.0
Hz, 3H, CMe), 2.42 (s, 3H, Ph-Me), 3.43 (s, 3H, OMe), 3.77
(dd, J ) 9.6, 5.1 Hz, 1H, 2-H), 3.99 (qd, J ) 6.0, 5.1 Hz, 1H,
3-H), 5.21 (d, J ) 9.6 Hz, 1H, NH), 7.27-7.30 (m, 2H, Ph),
7.69-7.72 (m, 2H, Ph); 13C NMR (75 MHz, CDCl3) δ -5.14,
-4.50, 17.8, 20.7, 21.5, 25.5 (3C), 52.0, 61.8, 70.5, 127.3 (2C),
129.6 (2C), 136.6, 143.6, 170.2; MS (FAB) m/z 402 (MH+, 100);
HRMS (FAB) calcd C18H32NO5SSi (MH+) 402.1771, found
402.1761. Anal. Calcd for C18H31NO5SSi: C, 53.83; H, 7.78;
N, 3.49. Found: C, 53.86; H, 7.68; N, 3.48.
(2S,3R)-3-ter t-Bu t yld im et h ylsilyloxy-2-[N-(4-m et h yl-
p h en ylsu lfon yl)a m in o]bu ta n -1-ol (7). Diisobutylaluminum
hydride (1.0 M solution in toluene; 57 mL, 57 mmol) was added
dropwise to a stirred solution of the ester 6 (6.54 g, 16.3 mmol)
in a mixed solvent of toluene (27 mL) and CHCl3 (11 mL) at
-78 °C under nitrogen. Stirring was continued for 3 h at -50
°C, and saturated NH4Cl was added dropwise with stirring.
The mixture was made acidic with 4% HCl at 0 °C and
extracted with a mixed solvent of Et2O-EtOAc (1:1). The
extract was washed with water and brine, and dried over
MgSO4. Concentration under reduced pressure gave an oily
residue, which was purified by chromatography over silica gel
with hexane-EtOAc (3:1) to give 7 (3.90 g, 64% yield) as a
the azetidine 56 in good yield, the anti,syn-30 yielded 57
in 57% yield and elimination product 58 in 42% yield
(Scheme 10).
Stereochemistries of the azetidines 56 and 57 and (E)-
geometry of the homoallylic amine 58 were confirmed by
NOE analyses (see the Supporting Information).
As is revealed from these observations, highly substi-
tuted azetidines can be prepared from 2-ethynyl-1,3-
amino alcohols derived from 2-ethynylaziridines, under
the typical Mitsunobu conditions. However, yields of the
azetidine synthesis have proven to be dependent on the
structure of the starting amino alcohols.
colorless oil: [R]25 -24.1 (c 1.01, CHCl3); IR (KBr) cm-1 3520
D
(OH), 3282 (NHSO2), 1327 (NHSO2); 1H NMR (300 MHz,
CDCl3) δ 0.06 (s, 3H, SiMe), 0.08 (s, 3H, SiMe), 0.86 (s, 9H,
CMe3), 1.16 (d, J ) 6.6 Hz, 3H, CMe), 2.43 (s, 3H, Ph-Me),
2.77 (dd, J ) 9.9, 1.8 Hz, 1H, OH), 3.03 (qd, J ) 6.6, 3.3 Hz,
1H, 3-H), 3.25 (ddd, J ) 11.4, 9.9, 3.6 Hz, 1H, 1-CHH), 3.90
(ddd, J ) 11.4, 2.7, 1.8 Hz, 1H, 1-CHH), 4.03-4.11 (m, 1H,
2-H), 5.30 (d, J ) 8.1 Hz, 1H, NH), 7.29-7.32 (m, 2H, Ph),
7.44-7.77 (m, 2H, Ph); 13C NMR (75 MHz, CDCl3) δ -5.0,
-4.7, 17.8, 20.5, 21.5, 25.7 (3C), 58.4, 61.1, 72.2, 127.0 (2C),
129.8 (2C), 137.6, 143.5; MS (FAB) m/z 374 (MH+, 100); HRMS
(FAB) calcd C17H32NO4SSi (MH+) 374.1821, found 374.1816.
(3S,4R)-4-ter t-Bu t yld im et h ylsilyloxy-3-[N-(4-m et h yl-
p h en ylsu lfon yl)a m in o]-1-p en tyn e (8). To a stirred solution
of oxalyl chloride (1.17 mL, 13.4 mmol) in CH2Cl2 (30 mL) at
-78 °C under nitrogen was added dropwise a solution of
DMSO (3.65 mL, 51.4 mmol) in CH2Cl2 (5 mL). After 30 min,
a solution of the alcohol 7 (3.84 g, 10.3 mmol) in CH2Cl2 (10
mL) was added to the above reagent at -78 °C, and the
mixture was stirred for 1 h. Diisopropylethylamine (12.2 mL,
72.0 mmol) was added to the above solution at -78 °C, and
the mixture was stirred for 30 min with warming to 0 °C. The
mixture was made acidic with 1 N HCl, and the whole was
extracted with Et2O. The extract was washed successively with
water and brine and dried over MgSO4. The filtrate was
concentrated under reduced pressure to give a crude aldehyde.
A mixture of dibromomethyltriphenylphosphonium bromide
(13.2 g, 25.7 mmol) and t-BuOK (2.77 g, 24.7 mmol) was
dissolved in THF (100 mL) at room temperature under
nitrogen. After the mixture was stirred for 5 min, a solution
Con clu sion
In conclusion, we have demonstrated a novel utility of
2-ethynylaziridines as a precursor of chiral carbanions
by umpolung with indium(I). Allenylindium reagents
bearing a protected amino group were effectively formed
by the treatment of 2-ethynylaziridines with InI, H2O,
and catalytic Pd(0). Reaction of the allenylindium, pre-
pared from 2,3-trans-2-ethynylaziridines, with aldehydes
afford syn,syn-2-ethynyl-1,3-amino alcohols selectively,
while the reagents from 2,3-cis-aziridines give anti,syn
isomers in high selectivities. This is the first example to
demonstrate the utility of allenylindium reagents bearing
an amino group as chiral carbanions. Highly substituted
azetidines bearing three chiral centers are easily syn-
thesized from the resulting amino alcohols under the
typical Mitsunobu conditions.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points are uncorrected. 1H
NMR spectra were recorded in CDCl3. Chemical shifts are
reported in parts per million downfield from internal Me4Si
(s ) singlet, d ) doublet, dd ) double doublet, ddd ) doublet
of double doublet, t ) triplet, q ) quartet, m ) multiplet).

2-Ethynylaziridines as Chiral Carbon Nucleophiles
J . Org. Chem., Vol. 66, No. 5, 2001 1873
of the above crude aldehyde in THF (10 mL) was added to this
brown reagent at room temperature, and the mixture was
stirred for 15 min. Additional t-BuOK (5.77 g, 51.4 mmol) was
then added at room temperature, stirring was continued for
15 min, and brine was then added. The whole was extracted
with Et2O, and the extract was dried over MgSO4. The filtrate
was concentrated under reduced pressure to give an oily
residue, which was flash chromatographed on a silica gel
column with hexane-EtOAc (6:1) to give 8 (1.68 g, 44% yield)
(2C), 137.4, 143.4; MS (FAB) m/z 310 (100), 368 (MH+, 97);
HRMS (FAB) calcd C18H29NO3SSi (MH+) 368.1716, found
368.1710. Anal. Calcd for C18H29NO3SSi: C, 58.82; H, 7.95;
N, 3.81. Found: C, 58.53; H, 7.80; N, 3.78.
(3R,4R)-4-Hyd r oxy-3-[N-(4-m eth ylp h en ylsu lfon yl)a m i-
n o]-1-p en tyn e (12). By a procedure identical with that
described for the synthesis of 9 from 8, 11 (3.00 g, 8.16 mmol)
was converted into 12 (1.85 g, 90% yield) as colorless crystals:
mp 112 °C (EtOAc-hexane); [R]26 -82.2 (c 1.00, CHCl3); IR
D
as a colorless oil: [R]25 +59.2 (c 1.00, CHCl3); IR (KBr) cm-1
(KBr) cm-1 3521 (OH), 3269 (NHSO2), 2119 (CtC), 1327
D
3278 (NHSO2), 2121 (CtC), 1336 (NHSO2); 1H NMR (300
MHz, CDCl3) δ 0.06 (s, 6H, SiMe2), 0.87 (s, 9H, CMe3), 1.21
(d, J ) 6.0 Hz, 3H, CMe), 2.07 (d, J ) 2.1 Hz. 1H, CtCH),
2.43 (s, 3H, Ph-Me), 3.91-4.00 (m, 2H, 3-H and 4-H), 4.77 (d,
J ) 8.1 Hz, 1H, NH), 7.29-7.31 (m, 2H, Ph), 7.76-7.79 (m,
2H, Ph); 13C NMR (75 MHz, CDCl3) δ -4.82, -4.43, 18.0, 19.9,
21.5, 25.7 (3C), 51.7, 70.4, 73.7, 79.0, 127.4 (2C), 129.5 (2C),
137.2, 143.5; MS (FAB) m/z 368 (MH+, 100); HRMS (FAB)
calcd C18H30NO3SSi (MH+) 368.1716, found 368.1721.
(NHSO2); H NMR (300 MHz, CDCl3) δ 1.28 (d, J ) 6.0 Hz,
1
3H, CMe), 2.12 (d, J ) 1.8 Hz, 1H, CtCH), 2.43 (s, 3H, Ph-
Me), 2.44-2.50 (m, 1H, OH), 3.84-3.95 (m, 2H, 3-H and 4-H),
5.10 (d, J ) 7.5 Hz, 1H, NH), 7.27-7.30 (m, 2H, Ph), 7.77-
7.80 (m, 2H, Ph); 13C NMR (75 MHz, CDCl3) δ 18.7, 21.5, 51.7,
70.0, 73.9, 79.7, 127.4 (2C), 129.5 (2C), 136.8, 143.7; MS (EI)
m/z 254 (MH+, 0.3), 54 (100). Anal. Calcd for C12H15NO3S: C,
56.90; H, 5.97; N, 5.53. Found: C, 56.80; H, 5.97; N, 5.48.
(2R,3S)-2-Eth yn yl-3-m eth yl-N-(4-m eth ylph en ylsu lfon yl)-
a zir id in e (4f). By a procedure identical with that described
for the synthesis of 3f from 9, 12 (2.00 g, 7.90 mmol) was
converted into 4f (1.53 g, 82% yield) as colorless crystals: mp
57 °C (EtOAc-hexane); [R]26D -91.9 (c 0.99, CHCl3); IR (KBr)
cm-1 3288 (NHSO2), 2129 (CtC), 1327 (NHSO2); 1H NMR (300
MHz, CDCl3) δ 1.35 (d, J ) 5.4 Hz, 3H, CMe), 2.20 (d, J ) 1.8
Hz, 1H, CtCH), 2.46 (s, 3H, Ph-Me), 3.01 (dq, J ) 6.9, 5.4 Hz,
1H, 3-H), 3.31 (dd, J ) 6.9, 1.8 Hz, 1H, 2-H), 7.34-7.37 (m,
2H, Ph), 7.82-7.85 (m, 2H, Ph); 13C NMR (75 MHz, CDCl3) δ
13.3, 21.6, 33.6, 40.0, 72.7, 76.4, 127.8 (2C), 129.8 (2C), 134.7,
144.8; MS (EI) m/z 236 (MH+, 0.14), 80 (100). Anal. Calcd for
(3S,4R)-4-Hyd r oxy-3-[N-(4-m eth ylp h en ylsu lfon yl)a m i-
n o]-1-p en tyn e (9). To a solution of the alkyne 8 (1.66 g, 4.53
mmol) in THF (20 mL) was added tetrabutylammonium
fluoride (1.0 M solution in THF; 5.44 mL, 5.44 mmol) at 0 °C
with stirring, and the mixture was stirred for 1.5 h. The
mixture was made acidic with 4% HCl, the whole was
extracted with a mixed solvent of EtOAc-Et2O (3:1), and the
extract was washed with water, saturated NaHCO3, and brine
and dried over MgSO4. The filtrate was concentrated under
reduced pressure to give an oily residue, which was purified
by column chromatography over silica gel with hexane-EtOAc
(1:1) to give 9 (872 mg, 76% yield) as colorless crystals: mp
141 °C (EtOAc-hexane); [R]26D +66.4 (c 1.00, CHCl3); IR (KBr)
cm-1 3512 (OH), 3267 (NHSO2), 2112 (CtC), 1319 (NHSO2);
1H NMR (300 MHz, CDCl3) δ 1.27 (d, J ) 6.3 Hz, 3H, CMe),
2.09 (d, J ) 8.1 Hz, 1H, OH), 2.14 (d, J ) 2.4 Hz, 1H, CtCH),
2.43 (s, 3H, Ph-Me), 3.87-3.97 (m, 1H, 4-H), 4.05 (ddd, J )
9.3, 2.7, 2.4 Hz, 1H, 3-H), 5.24 (d, J ) 9.3 Hz, 1H, NH), 7.30-
7.32 (m, 2H, Ph), 7.77-7.80 (m, 2H, Ph); 13C NMR (75 MHz,
CDCl3) δ 19.5, 21.6, 51.6, 69.8, 74.7, 78.2, 127.4 (2C), 129.6
(2C), 137.1, 143.7; MS (FAB) m/z 254 (MH+, 21), 136 (100);
C
12H13NO2S: C, 61.25; H, 5.57; N, 5.95. Found: C, 61.19; H,
5.62; N, 5.93.
Gen er a l P r oced u r e for Syn th esis of 2-Eth yn yl-1,3-
a m in o Alcoh ols fr om 2-Eth yn yla zir id in es. Syn th esis of
(3R,4R,5S)-4-Eth yn yl-2-m eth yl-5-[N-(2,4,6-tr im eth ylp h en -
ylsu lfon yl)a m in o]-6-p h en ylh exa n -3-ol (15). To a solution
of the aziridine 3c (102 mg, 0.3 mmol) in a mixed solvent of
THF (2.4 mL) and HMPA (0.6 mL) were added H2O (5 µL, 0.3
mmol), isobutyraldehyde (41 µL, 0.45 mmol), InI (94.3 mg, 0.39
mmol) and Pd(PPh3)4 (17.3 mg, 5 mol %, 0.015 mmol) succes-
sively at room temperature. The mixture was stirred for 4 h
at this temperature and quenched with 1 N HCl (1 mL). The
whole was extracted with Et2O, and the extract was washed
with water and dried over MgSO4. Usual workup followed by
flash chromatography over silica gel with hexane-EtOAc (5:2)
gave 15 (76.3 mg, 62% yield): colorless needles; mp 123 °C
HRMS (FAB) Calcd
C
12H16NO3S (MH+) 254.0851, found
254.0849. Anal. Calcd for C12H15NO3S: C, 56.90; H, 5.97; N,
5.53. Found: C, 56.68; H, 5.93; N, 5.49.
(2S,3S)-2-E t h yn yl-3-m et h yl-N-(4-m et h ylp h en ylsu lfo-
n yl)a zir id in e (3f). To a mixture of the amino alcohol 9 (780
mg, 3.08 mmol) and PPh3 (969 mg, 3.70 mmol) in THF (5 mL)
was added dropwise diethyl azodicarboxylate (0.59 mL, 3.70
mmol) at 0 °C with stirring, and the mixture was stirred for
30 min. The mixture was concentrated under reduced pressure,
and the residue was purified by column chromatography over
silica gel with hexane-EtOAc (3:1) to give 3f (565 mg, 78%
yield) as colorless crystals; mp 91-92 °C (EtOAc-hexane);
[R]26D +72.9 (c 1.00, CHCl3); IR (KBr) cm-1 3271 (NSO2), 2127
(hexane-Et2O); [R]23 +7.30 (c 1.00, CHCl3); IR (KBr) cm-1
D
3547 (OH), 3296 (NHSO2), 2114 (CtC), 1333 (NHSO2); 1H
NMR (270 MHz, CDCl3) δ 0.55 (d, J ) 6.8 Hz, 3H, CMe), 0.64
(d, J ) 6.8 Hz, 3H, CMe), 1.40-1.49 (m, 1H, 2-H), 2.10 (d, J
) 5.4 Hz, 1H, OH), 2.29 (s, 3H, Ph-Me), 2.33 (d, J ) 2.7 Hz,
1H, CtCH), 2.62 (ddd, J ) 5.9, 2.7, 2.4 Hz, 1H, 4-H), 2.66 (s,
6H, 2 × Ph-Me), 2.82 (dd, J ) 13.5, 9.7 Hz, 1H, 6-CHH), 2.88
(dd, J ) 13.5, 5.1 Hz, 1H, 6-CHH), 3.22 (ddd, J ) 5.9, 5.4, 5.4
Hz, 1H, 3-H), 3.44-3.51 (m, 1H, 5-H), 5.21 (d, J ) 8.1 Hz, 1H,
NH), 6.95 (s, 2H, Ph), 7.03-7.06 (m, 2H, Ph), 7.17-7.26 (m,
3H, Ph); 13C NMR (67.8 MHz, CDCl3) δ 15.5, 19.5, 21.0, 23.2
(2C), 30.9, 38.6, 40.5, 56.3, 74.8, 75.5, 80.2, 126.7, 128.6 (2C),
128.8 (2C), 132.0 (2C), 134.4, 137.0, 138.6 (2C), 142.2. MS (EI)
m/z 415 (M + 2, 0.2), 250 (100). Anal. Calcd for C24H31NO3S:
C, 69.70; H, 7.56; N, 3.39. Found: C, 69.41; H, 7.40; N, 3.33.
(3R,4R,5S)-4-Eth yn yl-2,6-d im eth yl-5-[N-(2,4,6-tr im eth -
ylp h en ylsu lfon yl)a m in o]h ep ta n -3-ol (16). By a procedure
identical with that described for the synthesis of 15 from 3c,
3a (58.3 mg, 0.2 mmol) was converted into 16 (30.7 mg, 42%
yield): colorless oil; [R]23D -31.4 (c 1.13, CHCl3); IR (KBr) cm-1
3525 (OH), 3305 (NHSO2), 2114 (CtC), 1328 (NHSO2); 1H
NMR (270 MHz, CDCl3) δ 0.70 (d, J ) 6.8 Hz, 3H, CMe), 0.85
(d, J ) 6.8 Hz, 3H, CMe), 0.89 (d, J ) 6.8 Hz, 6H, 2 × CMe),
1.59-1.71 (m, 1H, Me2CH), 1.78-1.91 (m, 1H, Me2CH), 2.20
(d, J ) 4.3 Hz, 1H, OH), 2.25 (d, J ) 1.6 Hz, 1H, CtCH), 2.26
(s, 3H, Ph-Me), 2.62 (s, 6H, 2 × Ph-Me), 2.72-2.78 (m, 1H,
4-H), 3.01-3.07 (m, 1H, 3-H), 3.23 (ddd, J ) 9.2, 6.8, 2.4 Hz,
1H, 5-H), 4.98 (d, J ) 9.2 Hz, 1H, NH), 6.94 (s, 2H, Ph); 13C
NMR (67.8 MHz, CDCl3) δ 15.6, 19.2, 19.3, 19.6, 21.0, 23.1
1
(CtC), 1331 (NSO2); H NMR (300 MHz, CDCl3) δ 1.44 (d, J
) 5.7 Hz, 3H, CMe), 2.38 (d, J ) 1.8 Hz, 1H, CtCH), 2.45 (s,
3H, Ph-Me), 3.03 (dd, J ) 4.5, 1.8 Hz, 1H, 2-H), 3.13 (qd, J )
5.7, 4.5 Hz, 1H, 3-H), 7.33-7.36 (m, 2H, Ph), 7.86-7.88 (m,
2H, Ph); 13C NMR (75 MHz, CDCl3) δ 15.4, 21.6, 35.4, 44.7,
73.8, 77.1, 127.6 (2C), 129.6 (2C), 136.7, 144.4. MS (FAB) m/z
236 (MH+, 100); HRMS (FAB) Calcd C12H14NO2S (MH+)
236.0745, found 236.0727. Anal. Calcd for C12H13NO2S: C,
61.25; H, 5.57; N, 5.95. Found: C, 61.10; H, 5.59; N, 5.87.
(3R,4R)-4-ter t-Bu t yld im et h ylsilyloxy-3-[N-(4-m et h yl-
p h en ylsu lfon yl)a m in o]-1-p en tyn e (11). By a procedure
identical with that described for the synthesis of 8 from 7, 10
(7.00 g, 18.7 mmol) was converted into 11 (3.27 g, 48%) as
colorless crystals: mp 73 °C (hexane); [R]26 -58.7 (c 1.03,
D
CHCl3); IR (KBr) cm-1 3278 (NHSO2), 2121 (CtC), 1331
(NHSO2); 1H NMR (300 MHz, CDCl3) δ 0.07 (s, 6H, SiMe2),
0.89 (s, 9H, CMe3), 1.21 (d, J ) 6.3 Hz, 3H, CMe), 2.02 (d, J )
2.4 Hz. 1H, CtCH), 2.43 (s, 3H, Ph-Me), 3.92 (ddd, J ) 8.7,
2.7, 2.4 Hz, 1H, 3-H), 3.97 (qd, J ) 6.3, 2.7 Hz, 1H, 4-H), 4.84
(d, J ) 8.7 Hz, 1H, NH), 7.28-7.31 (m, 2H, Ph), 7.76-7.79
(m, 2H, Ph); 13C NMR (75 MHz, CDCl3) δ -4.79, -4.55, 18.0,
20.2, 21.5, 25.8 (3C), 51.2, 70.6, 72.7, 81.0, 127.3 (2C), 129.4

1874 J . Org. Chem., Vol. 66, No. 5, 2001
Ohno et al.
(2C), 30.4, 33.3, 39.1, 59.1, 74.8, 76.0, 81.2, 131.8 (2C), 135.7,
138.0 (2C), 141.7; MS (FAB) m/z 366 (MH+, 100); HRMS (FAB)
calcd C20H32NO3S (MH+) 366.2103, found 366.2113.
(3S,4S,5S)-4-Eth yn yl-2-m eth yl-5-[N-(2,4,6-tr im eth ylph en -
ylsu lfon yl)a m in o]-6-p h en ylh exa n -3-ol (24). By a procedure
identical with that described for the synthesis of 15 from 3c,
4c (67.9 mg, 0.26 mmol) was converted into 24 (60.0 mg, 72%
yield): colorless oil; [R]24D -10.5 (c 1.00, CHCl3); IR (KBr) cm-1
3516 (OH), 3296 (NHSO2), 2116 (CtC), 1319 (NHSO2); 1H
NMR (300 MHz, CDCl3) δ 0.78 (d, J ) 6.9 Hz, 3H, CMe), 1.00
(d, J ) 6.6 Hz, 3H, CMe), 1.79-1.93 (m, 1H, 2-H), 2.17 (d, J
) 2.4 Hz, 1H, CtCH), 2.28 (s, 3H, Ph-Me), 2.53-2.56 (m, 1H,
OH), 2.56 (s, 6H, 2 × Ph-Me), 2.61 (ddd, J ) 7.5, 2.4, 2.4 Hz,
1H, 4-H), 2.86 (dd, J ) 14.1, 5.7 Hz, 1H, PhCHH), 3.04 (dd, J
) 14.1, 6.0 Hz, 1H, PhCHH), 3.36-3.42 (m, 1H, 3-H), 3.74-
3.84 (m, 1H, 5-H), 5.05 (d, J ) 9.3 Hz, 1H, NH), 6.87 (s, 2H,
Ph), 7.02-7.20 (m, 5H, Ph); 13C NMR (75 MHz, CDCl3) δ 18.9,
19.1, 20.8, 23.3 (2C), 32.3, 38.7, 39.9, 55.6, 74.1, 74.5, 80.8,
126.7, 128.5 (2C), 129.3 (2C), 132.0 (2C), 134.5, 136.2, 138.5
(2C), 142.0; MS (FAB) m/z 414 (MH+, 100); HRMS (FAB) calcd
C24H32NO3S (MH+) 414.2103, found 414.2101.
(3R,4R,5R)-6-ter t-Bu t yld im et h ylsilyloxy-4-et h yn yl-2-
m eth yl-5-[N-(2,4,6-tr im eth ylph en ylsu lfon yl)am in o]h exan -
3-ol (19). By a procedure identical with that described for the
synthesis of 15 from 3c, 3e (78.7 mg, 0.2 mmol) was converted
into 19 (64.0 mg, 68% yield): colorless oil; [R]27D +15.6 (c 1.43,
CHCl3); IR (KBr) cm-1 3552 (OH), 3311 (NHSO2), 2116 (Ct
C), 1335 (NHSO2); 1H NMR (270 MHz, CDCl3) δ -0.01 (s, 3H,
SiMe), 0.00 (s, 3H, SiMe), 0.76 (d, J ) 6.8 Hz, 3H, CMe), 0.84
(s, 9H, CMe3), 0.90 (d, J ) 6.8 Hz, 3H, CMe), 1.56-1.68 (m,
1H, 2-H), 2.14 (d, J ) 2.4 Hz, 1H, CtCH), 2.28-2.30 (m, 1H,
OH), 2.30 (s, 3H, Ph-Me), 2.65 (s, 6H, 2 × Ph-Me), 3.02-3.07
(m, 1H, 4-H), 3.12-3.18 (m, 1H, 3-H), 3.33-3.41 (m, 1H, 5-H),
3.51 (dd, J ) 9.7, 7.3 Hz, 1H, 6-CHH), 3.66 (dd, J ) 9.7, 3.8
Hz, 1H, 6-CHH), 5.11 (d, J ) 8.4 Hz, 1H, NH), 6.96 (s, 2H,
Ph); 13C NMR (67.8 MHz, CDCl3) δ -5.53, -5.48, 17.3, 18.2,
19.3, 21.0, 23.2 (2C), 25.8 (3C), 31.6, 37.6, 55.5, 62.8, 74.0, 75.4,
80.1, 131.9 (2C), 134.2, 138.8 (2C), 142.3; MS (FAB) m/z 468
(MH+, 100), 119 (74); HRMS (FAB) calcd C24H42NO4SSi (MH+)
468.2604, found 468.2605.
(3S,4S,5R)-6-ter t-Bu t yld im et h ylsilyloxy-4-et h yn yl-2-
m eth yl-5-[N-(2,4,6-tr im eth ylph en ylsu lfon yl)am in o]h exan -
3-ol (26). By a procedure identical with that described for the
synthesis of 15 from 3c, 4e (78.7 mg, 0.2 mmol) was converted
into 26 (65.8 mg, 70% yield): colorless oil; [R]28D -5.91 (c 0.930,
CHCl3); IR (KBr) cm-1 3541 (OH), 3311 (NHSO2), 2118 (Ct
(3R,4R,5S)-4-Eth yn yl-2-m eth yl-5-[N-(4-m eth ylp h en yl-
su lfon yl)a m in o]h exa n -3-ol (20) a n d Its (3S,4S,5S)-Isom er
(21). By a procedure identical with that described for the
synthesis of 15 from 3c, 3f (47.1 mg, 0.2 mmol) was converted
into 20 (41.1 mg, 73% yield) and 21 (3.1 mg, 6% yield).
1
C), 1326 (NHSO2); H NMR (270 MHz, CDCl3) δ 0.02 (s, 3H,
SiMe), 0.03 (s, 3H, SiMe), 0.86 (d, J ) 5.9 Hz, 3H, CMe), 0.87
(s, 9H, CMe3), 1.08 (d, J ) 6.5 Hz, 3H, CMe), 1.91-2.03 (m,
1H, 2-H), 2.08 (d, J ) 2.4 Hz, 1H, CtCH), 2.31 (s, 3H, Ph-
Me), 2.64 (s, 6H, 2 × Ph-Me), 2.74 (ddd, J ) 10.3, 2.4, 2.4 Hz,
1H, 4-H), 2.98 (dd, J ) 10.3, 3.2 Hz, 1H, 6-CHH), 3.22 (d, J )
5.9 Hz, 1H, OH), 3.24-3.36 (m, 1H, 5-H), 3.60 (ddd, J ) 9.5,
5.9, 2.4 Hz, 1H, 3-H), 3.89 (dd, J ) 10.3, 0.8 Hz, 1H, 6-CHH),
5.43 (d, J ) 9.7 Hz, 1H, NH), 6.97 (s, 2H, Ph); 13C NMR (67.8
MHz, CDCl3) δ -5.56, -5.45, 18.3, 18.9, 20.1, 21.0, 23.0 (2C),
25.8 (3C), 31.9, 37.9, 54.5, 61.7, 73.0, 73.8, 80.7, 132.0 (2C),
133.9, 138.6 (2C), 142.5; MS (FAB) m/z 468 (MH+, 100), 119
(78); HRMS (FAB) calcd C24H42NO4SSi (MH+) 468.2604, found
468.2585.
Compound 20: colorless crystals; mp 114-115 °C (EtOAc-
hexane); [R]26D -13.5 (c 1.00, CHCl3); IR (KBr) cm-1 3535 (OH),
3236 (NHSO2), 2119 (CtC), 1319 (NHSO2); 1H NMR (300
MHz, CDCl3) δ 0.84 (d, J ) 6.9 Hz, 3H, CMe), 0.91 (d, J ) 6.6
Hz, 3H, CMe), 1.18 (d, J ) 6.6 Hz, 3H, CMe), 1.67-1.78 (m,
1H, 2-H), 2.08 (d, J ) 6.6 Hz, 1H, OH), 2.22 (d, J ) 2.7 Hz,
1H, CtCH), 2.43 (s, 3H, Ph-Me), 2.58 (ddd, J ) 3.9, 3.9, 2.7
Hz, 1H, 4-H), 3.21 (ddd, J ) 6.6, 6.6, 3.9 Hz, 1H, 3-H), 3.44-
3.49 (m, 1H, 5-H), 5.08 (d, J ) 7.2 Hz, 1H, NH), 7.30-7.33
(m, 2H, Ph), 7.76-7.79 (m, 2H, Ph); 13C NMR (75 MHz, CDCl3)
δ 17.2, 19.3, 20.7, 21.5, 31.8, 42.3, 51.3, 74.7, 76.2, 79.6, 127.2
(2C), 129.6 (2C), 137.5, 143.5. MS (FAB) m/z 310 (MH+, 67),
69 (100); HRMS (FAB) calcd C16H24NO3S (MH+) 310.1477,
found 310.1479. Anal. Calcd for C16H23NO3S: C, 62.11; H, 7.49;
N, 4.53. Found: C, 61.86; H, 7.36; N, 4.50.
Compound 21: colorless crystals; mp 173 °C (EtOAc-
hexane); [R]26D -64.4 (c 0.99, CHCl3); IR (KBr) cm-1 3439 (OH),
3288 (NHSO2), 2116 (CtC), 1317 (NHSO2); 1H NMR (300
MHz, CDCl3) δ 0.86 (d, J ) 6.6 Hz, 3H, CMe), 1.02 (d, J ) 6.6
Hz, 3H, CMe), 1.10 (d, J ) 6.3 Hz, 6H, CMe), 1.81-1.93 (m,
1H, 2-H), 2.11 (d, J ) 2.4 Hz, 1H, CtCH), 2.44 (s, 3H, Ph-
Me), 2.48 (ddd, J ) 7.4, 2.4, 2.4 Hz, 1H, 4-H), 2.63 (d, J ) 6.6
Hz, 1H, OH), 3.46-3.59 (m, 2H, 3-H and 5-H), 4.59 (d, J )
9.3 Hz, 1H, NH), 7.31-7.34 (m, 2H, Ph), 7.56-7.78 (m, 2H,
Ph); 13C NMR (75 MHz, CDCl3) δ 19.0 (2C), 19.7, 21.5, 31.9,
43.1, 50.5, 73.5, 74.3, 80.6, 127.1 (2C), 129.8 (2C), 137.4, 143.7;
MS (FAB) m/z 310 (MH+, 100); HRMS (FAB) calcd C16H24NO3S
(MH+) 310.1477, found 310.1500.
(2S,3S,4S)-2-ter t-Bu tyld im eth ysilyloxy-3-eth yn yl-4-[N-
(4-m eth oxy-2,3,6-tr im eth ylph en ylsu lfon yl)am in o]-5-ph en -
ylp en ta n e (34) a n d Its (2R,3S,4S)-Isom er (35). By a
procedure identical with that described for the preparation of
15 from 3c, the aziridine 4d (73.9 mg, 0.2 mmol) was converted
into an inseparable mixture of 32 and 33 (73.9 mg, 75%; 32:
1
33 ) 88:12, H NMR) by treatment with Pd(PPh3)4 (11.6 mg,
0.01 mmol), InI (62.8 mg, 0.26 mmol), MeCHO (17 µL, 0.3
mmol) and H2O (4 µL, 0.2 mmol) in a mixed solvent of THF
(0.8 mL) and HMPA (0.2 mL). To a stirred solution of the above
diastereomixture (38 mg, 0.0914 mmol) in DMF (1 mL) were
added imidazole (15.6 mg, 0.229 mmol) and tert-butyldimeth-
ylsilyl chloride (13.4 mg, 0.11 mmol) at room temperature. The
mixture was stirred at room temperature for 48 h and was
made acidic with 0.5 N HCl. The whole was extracted with
Et2O and the extract was washed with water and dried
(MgSO4). Usual workup followed by flash chromatography over
silica gel with hexane-CHCl3-EtOAc (15:6:1) gave, in order
of elution, 34 (42.1 mg, 87% yield) and 35 (4.6 mg, 10% yield).
Compound 34: colorless needles; mp 138 °C (hexane-Et2O);
[R]18D -20.6 (c 0.96, CHCl3); IR (KBr) cm-1 3307 (NHSO2), 2114
(CtC), 1308 (NHSO2); 1H NMR (270 MHz, CDCl3) δ -0.01 (s,
3H, SiMe), 0.00 (s, 3H, SiMe), 0.79 (s, 9H, CMe3), 1.15 (d, J )
6.2 Hz, 3H, 1-Me), 2.00 (s, 3H, Ph-Me), 2.05 (d, J ) 2.4 Hz,
1H, CtCH), 2.30 (s, 3H, Ph-Me), 2.59 (s, 3H, Ph-Me), 2.61-2.64
(m, 1H, 3-H), 2.83 (dd, J ) 14.3, 7.0 Hz, 1H, 5-CHH), 2.89
(dd, J ) 14.3, 5.4 Hz, 1H, 5-CHH), 3.61-3.70 (m, 1H, 4-H),
3.78 (s, 3H, OMe), 3.92-4.00 (m, 1H, 2-H), 5.49 (d, J ) 6.8 Hz,
1H, NH), 6.45 (s, 1H, Ph), 6.89-6.93 (m, 2H, Ph), 7.03-7.05
(m, 3H, Ph); 13C NMR (67.8 MHz, CDCl3) δ -4.53, -4.22, 12.1,
18.1, 18.2, 20.9, 24.8, 25.8 (3C), 37.9, 43.5, 55.0, 55.5, 69.2,
73.1, 81.8, 111.8, 124.9, 126.2, 127.9 (2C), 129.2 (2C), 129.5,
136.8, 138.1, 139.1, 158.9. Anal. Calcd for C29H43NO4SSi: C,
65.74; H, 8.18; N, 2.64. Found: C, 65.82; H, 8.17; N, 2.67.
(3S,4S,5S)-4-Eth yn yl-2,6-d im eth yl-5-[N-(2,4,6-tr im eth -
ylp h en ylsu lfon yl)a m in o]h ep ta n -3-ol (22). By a procedure
identical with that described for the synthesis of 15 from 3c,
4a (87.4 mg, 0.3 mmol) was converted into 22 (64.7 mg, 59%
yield): colorless crystals; mp 66 °C (hexane-Et2O); [R]27D -35.1
(c 1.45, CHCl3); IR (KBr) cm-1 3537 (OH), 3302 (NHSO2), 2116
1
(CtC), 1313 (NHSO2); H NMR (270 MHz, CDCl3) δ 0.46 (d,
J ) 6.8 Hz, 3H, CMe), 0.82 (d, J ) 6.8 Hz, 3H, CMe), 0.86 (d,
J ) 6.8 Hz, 3H, CMe), 1.02 (d, J ) 6.5 Hz, 3H, CMe), 1.87-
2.01 (m, 1H, Me2CH), 2.09 (d, J ) 2.4 Hz, 1H, CtCH), 2.28-
2.35 (m, 1H, Me2CH), 2.29 (s, 3H, Ph-Me), 2.55 (d, J ) 9.5 Hz,
1H, OH), 2.64 (s, 6H, 2 × Ph-Me), 3.04-3.07 (m, 1H, 4-H),
3.34-3.40 (m, 1H, 3-H), 3.48 (ddd, J ) 10.3, 10.0, 3.0 Hz, 1H,
5-H), 4.73 (dd, J ) 10.3, 4.1 Hz, 1H, NH), 6.94 (s, 2H, Ph); 13
C
NMR (67.8 MHz, CDCl3) δ 15.8, 19.1, 19.8, 20.3, 21.0, 23.3
(2C), 29.7, 32.0, 40.5, 59.2, 73.1, 74.0, 80.8, 131.8 (2C), 135.3,
138.1 (2C), 142.0; MS (EI) m/z 367 (M + 2, 0.2), 254 (100).
Anal. Calcd for C20H31NO3S: C, 65.72; H, 8.55; N, 3.83.
Found: C, 65.44; H, 8.70; N, 3.61.
Compound 35: colorless oil; [R]21 -50.2 (c 0.235, CHCl3);
D
IR (KBr) cm-1 3307 (NHSO2), 2114 (CtC), 1308 (NHSO2); 1H
NMR (270 MHz, CDCl3) δ 0.03 (s, 3H, SiMe), 0.08 (s, 3H,

2-Ethynylaziridines as Chiral Carbon Nucleophiles
J . Org. Chem., Vol. 66, No. 5, 2001 1875
SiMe), 0.89 (s, 9H, CMe3), 1.33 (d, J ) 5.9 Hz, 3H, 1-Me), 1.98
(s, 3H, Ph-Me), 2.02 (s, 3H, Ph-Me), 2.23 (d, J ) 2.7 Hz, 1H,
CtCH), 2.57 (s, 3H, Ph-Me), 2.66 (dd, J ) 14.3, 11.3 Hz, 1H,
5-CHH), 2.95 (dd, J ) 14.3, 3.5 Hz, 1H, 5-CHH), 3.14 (ddd, J
) 9.2, 4.1, 2.7 Hz, 1H, 3-H), 3.81-3.93 (m, 2H, 2-H and 4-H),
3.85 (s, 3H, OMe), 4.57 (d, J ) 9.7 Hz, 1H, NH), 6.46 (s, 1H,
Ph), 6.85-6.87 (m, 2H, Ph), 6.98-7.12 (m, 3H, Ph); 13C NMR
(67.8 MHz, CDCl3) δ -4.35, -3.60, 12.0, 17.6, 18.1, 23.2, 24.9,
26.0 (3C), 35.5, 47.0, 52.4, 55.5, 68.8, 73.6, 82.0, 111.6, 124.8,
126.1, 128.0 (2C), 128.2, 128.7 (2C), 137.0, 138.6, 139.4, 159.0;
MS (FAB) m/z 530 (MH+, 100), 472 (93); HRMS (FAB) calcd
C29H44NO4SSi (MH+) 530.2761, found 530.2772.
cedure similar to that described for the synthesis of 3f from
9, 27 (15.5 mg, 0.032 mmol) was converted into 55 (13 mg,
87% yield) by treatment with PPh3 (34 mg, 0.13 mmol) and
diethyl azodicarboxylate (71 µL, 0.13 mmol) in THF at 0 °C
for 15 min: colorless oil; [R]27D +6.71 (c 0.65, CHCl3); IR (KBr)
cm-1 3292 (NSO2), 2119 (CtC), 1311 (NSO2); 1H NMR (500
MHz, CDCl3) δ 2.02 (s, 3H, Ph-Me), 2.37 (d, J ) 2.4 Hz, 1H,
CtCH), 2.49 (s, 3H, Ph-Me), 2.54 (s, 3H, Ph-Me), 3.35 (ddd, J
) 7.8, 6.9, 2.4 Hz, 1H, 3-H), 3.62 (dd, J ) 14.7, 10.8 Hz, 1H,
PhCHH), 3.70-3.76 (m, 1H, PhCHH), 3.74 (s, 3H, OMe), 4.88
(ddd, J ) 10.8, 7.8, 3.0 Hz, 1H, 4-H), 5.15 (d, J ) 6.9 Hz, 1H,
2-H), 6.26 (s, 1H, Ph), 7.04-7.39 (m, 10H, Ph); 13C NMR (75
MHz, CDCl3) δ 11.8, 18.0, 24.1, 35.26, 35.31, 55.4, 66.1, 71.0,
75.8, 80.2, 111.6, 124.8, 126.3, 126.7 (2C), 128.0 (2C), 128.2
(2C), 128.3, 129.1, 129.7 (2C), 137.3, 137.6, 139.2, 140.0, 159.4;
MS (FAB) m/z 460 (MH+, 5.1), 185 (100); HRMS (FAB) calcd
(4S,5R,6S)-5-Eth yn yl-4-isop r op yl-6-p h en yl-tetr a h yd r o-
1,3-oxa zin -2-on e (38). To a stirred suspension of NaH (5.6
mg, 0.14 mmol) in DMF (0.5 mL) under argon was added 37
(37 mg, 0.117 mmol) in dry THF (0.5 mL) at room temperature,
and the mixture was stirred for 1 h. The mixture was poured
into ice water (3 mL) saturated with NH4Cl, and the whole
was extracted with Et2O. The extract was washed with water,
and dried (MgSO4). Usual workup gave a crystalline mass,
which was recrystallized from hexane-CH2Cl2 to give 38 (12.5
C
28H30NO3S (MH+) 460.1946, found 460.1945.
(2S,4S)-3-Eth yn yl-2,4-d im eth yl-N-(4-m eth ylp h en ylsu l-
fon yl)a zetid in e (56). By a procedure similar to that described
for the synthesis of 3f from 9, 29 (13.3 mg, 0.047 mmol) was
converted into 56 (10 mg, 81% yield) by treatment with PPh3
(55.4 mg, 0.21 mmol) and diethyl azodicarboxylate (33 µL, 0.21
mmol) in THF at 0 °C for 10 min: colorless crystals; mp 72 °C
mg, 44% yield): colorless crystals; mp 233 °C; [R]27 -113 (c
D
0.550, CHCl3); IR (KBr) cm-1 3290 (NHCO), 2117 (CtC), 1704
(NHCO), 1394 (NHCO); 1H NMR (500 MHz, CDCl3) δ 1.01 (d,
J ) 6.0 Hz, 3H, CMe), 1.10 (d, J ) 6.0 Hz, 3H, CMe), 1.95-
2.03 (m, 1H, Me2CH), 2.07 (d, J ) 2.5 Hz, 1H, CtCH), 3.10-
3.11 (m, 1H, 5-H), 3.27 (dd, J ) 9.8, 3.7 Hz, 1H, 4-H), 5.35 (d,
J ) 1.8 Hz, 1H, 6-H), 5.69 (br s, 1H, NH), 7.34-7.41 (m, 3H,
Ph), 7.47-7.49 (m, 2H, Ph); 13C NMR (75 MHz, CDCl3) δ 18.6,
19.1, 30.8, 35.7, 60.8, 75.0, 75.4, 79.2, 126.1 (2C), 128.2 (2C),
128.5, 136.5, 153.3; MS (FAB) m/z 244 (MH+, 74), 116 (100);
HRMS (FAB) calcd C15H18NO2 (MH+) 244.1337, found 244.1325.
(4S,5S,6R)-5-Eth yn yl-4-isop r op yl-6-p h en yltetr a h yd r o-
1,3-oxa zin -2-on e (40). By a procedure identical with that
described for the synthesis of 38 from 37, 39 (40.0 mg, 0.126
mmol) was converted into 40 (13.0 mg, 42% yield) as colorless
(EtOAc-hexane); [R]24 +14.2 (c 0.34, CHCl3); IR (KBr) cm-1
D
1
3271 (NSO2), 2118 (CtC), 1336 (NSO2); H NMR (500 MHz,
CDCl3) δ 1.39 (d, J ) 6.0 Hz, 3H, CMe), 1.41 (d, J ) 6.0 Hz,
3H, CMe), 2.25 (d, J ) 2.5 Hz, 1H, CtCH), 2.44 (s, 3H, Ph-
Me), 3.00 (ddd, J ) 9.0, 6.5, 2.5 Hz, 1H, 3-H), 4.22 (dq, J )
6.5, 6.0 Hz, 1H, 2-H), 4.44 (dq, J ) 9.0, 6.0 Hz, 1H, 4-H), 7.30-
7.32 (m, 2H, Ph), 7.71-7.73 (m, 2H, Ph); 13C NMR (75 MHz,
CDCl3) δ 16.0, 20.2, 21.5, 33.3, 60.4, 64.9, 74.0, 79.7, 127.5
(2C), 129.6 (2C), 137.3, 144.1. MS (FAB) m/z 264 (MH+, 82),
136 (100); HRMS (FAB) calcd C14H18NO2S (MH+) 264.1058,
found 264.1063.
crystals: mp 195 °C (hexane-CHCl3); [R]25 +19.3 (c 0.500,
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research from the Ministry
of Education, Sports, and Culture, J apan, which is
gratefully acknowledged.
D
CHCl3); IR (KBr) cm-1 3234 (NHCO), 2123 (CtC), 1713
(NHCO), 1413 (NHCO); 1H NMR (500 MHz, CDCl3) δ 1.03 (d,
J ) 7.0 Hz, 3H, CMe), 1.06 (d, J ) 6.5 Hz, 3H, CMe), 1.94-
2.01 (m, 1H, Me2CH), 2.15 (d, J ) 2.5 Hz, 1H, CtCH), 3.12-
3.14 (m, 1H, 5H), 3.23 (ddd, J ) 5.5, 5.5, 2.5 Hz, 1H, 4-H),
5.42 (d, J ) 3.0 Hz, 1H, 6-H), 6.45 (br s, 1H, NH), 7.34-7.45
(m, 5H, Ph); 13C NMR (75 MHz, CDCl3) δ 17.4, 19.1, 31.5, 33.6,
59.1, 74.2, 76.3, 78.9, 126.4 (2C), 128.2 (2C), 128.5, 136.2, 154.0;
MS (FAB) m/z 244 (MH+, 86), 116 (100); HRMS (FAB) calcd
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for 17, 18, 23, 25, 27-31, 36, 37, 39, 53, 54, 57, and
58; NOE experiment of 56-58; 1H NMR spectra of all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
C
15H18NO2 (MH+) 244.1337, found 244.1348.
(2R,3R,4S)-4-Ben zyl-3-eth yn yl-N-(4-m eth oxy-2,3,6-tr i-
m eth ylp h en ylsu lfon yl)-2-p h en yla zetid in e (55). By a pro-
J O005756V